The aims of this project are to study the mechanisms of microtubule assembly and functioning and to further our understanding of the role of microtubules in immunologic processes, particularly immediate and delayed hypersensitivity. Initial experiments have involved the study of microtubule assembly in cell free preparations--i.e., supernatants prepared from rat brain (a good source of microtubule protein) and with partially purified tubulin. Particular emphasis is being placed on the relationship of cyclic AMP, a compound of known importance in immediate and delayed hypersensitivity, to microtubules. The effects of calcium on both microtubules assembly and functioning is also under study. Future experimentation will involve an in vitro model of immediate hypersensitivity: antigen-induced, IgE-mediated histamine release from human leukocytes (basophils). It is planned to apply knowledge gained from the study of microtubule assembly in cell-free systems to further define the role of microtubules in immediate hypersensitivity. While it is planned to place emphasis on immediate hypersensitivity, the microtubule system is also important in delayed hypersensitivity. Experiments will also be carried out therefore with an in vitro model of delayed hypersensitivity: target cell (mastocytoma) destruction (Cr51 release) by sensitized allogeneic mouse splenic lymphocytes. The long term goal of the project is the prevention or control of the symptoms of immediate hypersensitivity through control of the function of the microtubule system.